• Percent change in absolute range of motion from baseline to 6 months [ Designated as safety issue: Yes ]
  

• Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  
• Lung manifestations [ Designated as safety issue: Yes ]
  
• Percent of patients who are considered as responding or stable from the use of imatinib mesylate as assessed by range of motion measures [ Designated as safety issue: No ]
  
• Time to progression [ Designated as safety issue: No ]
  
• Time to response [ Designated as safety issue: No ]
  
• Correlative studies of tissue or blood samples [ Designated as safety issue: No ]
  
• MRI results [ Designated as safety issue: No ]
  
• Quality of life as assessed by Lee Symptom Scale and Chronic Graft-Versus-Host Disease Patient Self-Assessment Scale in patients 18 and over [ Designated as safety issue: No ]
  
• Rehabilitative and functional changes as assessed by measures of range of motion, grip strength, and walk time as well as the Human Activity Profile for patients 18 and over [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To investigate whether imatinib mesylate results in clinical improvement in skin fibrosis as measured by range of motion assessment of affected joints in pediatric and adult patients with sclerodermatous chronic graft-versus-host disease (ScGVHD).

Secondary

• To assess the toxicity of this drug in these patients.
• To establish outcome criteria for the evaluation of ScGVHD in these patients using multi-modality objective and subjective assessments, including magnetic resonance imaging, skin scoring, and patient self-reported measures.
• To correlate biomarkers of disease activity with response in patients treated with this drug.
• To assess quality of life and functional measures of disease activity in these patients and to evaluate changes in these measures during the course of therapy.
• To evaluate the response of other organ manifestations affected by cGVHD after treatment with this drug.

OUTLINE: Patients receive oral imatinib mesylate once daily on days 1-28. Treatment repeats every 28 days for up to 6 months following maximal response or a total of 2 years in the absence of disease progression or unacceptable toxicity. Patients requiring additional systemic therapy for control of chronic graft-versus-host disease (cGVHD) are removed from study.

Patients undergo blood sample collection at baseline and periodically during study for laboratory correlative studies. Samples are analyzed for antibody binding and functional activation status of PDGFR by FACS analysis; APC, stromal, and T-cell-derived cytokine mRNA, and T-cell lineage-specific transcription factors by RT-PCR; circulating TGF-β levels (i.e., active and latent) by ELISA and bioassay; TGF-β response and leukocyte (i.e., T- and B-cell) expression of TGF-β1, TGF-β receptors, and phospho-rSmad by FACS analysis; circulating IL-13 and IL-13rα2 levels by ELISA; and leukocyte (i.e., T- and B-cell) production of IL-13 and IL-13R2 by ELISA and FACS analysis. Some patients also undergo tissue sample collection at baseline and at 6 months. Tissue specimens are analyzed for phosphorylated-PDGFR by immunohistochemical staining; T-cell subsets (i.e., CM, EM, EMRA, CD4, CD8) by confocal microscopy; cytokine mRNA and T-cell lineage-specific transcription factors by RT-PCR; and for TGF-β ligands and receptor-activated Smad proteins by immunohistochemical staining. Antibodies specific for phosphorylated Smad proteins will be used as a biochemical marker for active signaling.

Formalin-fixed biopsy specimens are analyzed for IL-13, IL-13Rα1, and IL-13Rα2 by immunohistochemical staining and fresh biopsies may also be used to prepare mRNA for real-time PCR analysis of IL- 13, IL-13Rα1, and IL-13Rα2.

After completion of study therapy, patients are followed 3 months for 1 year.